Optimizing oral medications for children

Active pharmaceutical ingredients that taste bitter and/or irritate the mouth and throat are aversive to children as well as many adults. Effective methods of avoiding unpleasant tastes for adults (eg, encapsulating the medicine in pill, capsule, or tablet form) are problematic because many children cannot or will not swallow these. The unpalatable flavor of the medicine can thwart the benefits of even the most powerful of drugs. Failure to consume medication may do the child harm and can even be life-threatening.

This article provides an overview of the current knowledge of the sensory capabilities and preferences of children as it relates to flavor, defined here as the combined input of taste, smell, and chemical irritation. The methods used to evaluate flavor perception in children are reviewed. Recent scientific advances are summarized that shed light on why the bitter taste of oral pharmaceuticals is an ongoing formulation problem and how discoveries of novel flavor molecules and modulators of bitter tastes hold considerable promise for the future. Alternative methods for evaluation of the palatability of medicines are described.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development sponsored a Pediatric Formulation Initiative workshop on December 6 and 7, 2005, in Bethesda, Maryland. Information for this article was gathered from literature reviews that were then discussed during this workshop as well as during several conference calls with the Taste and Flavor Working Group members. Terms for the MEDLINE search (1970-2007) included infant, children, taste, olfaction/smell, flavor, chemical senses, palatability, sensory testing, pharmaceutical, and medicines.

Children have well-developed sensory systems for detecting tastes, smells, and chemical irritants, and their rejection of unpalatable medications is a reflection of their basic biology. Sugars, salt, and other substances reportedly reduce the bitterness of several pharmaceuticals. Adding pleasant flavor volatiles such as bubble gum may help induce children to consume a medicine, but such volatile compounds are not effective in suppressing the strong bitter tastes associated with some medications. Also, because individual experiences and culture mainly determine which odors are attractive, a universally appealing volatile flavoring agent may be difficult to identify. Sensory panelists who are sensitive to the pediatric palate, which is different from adults, and new techniques involving animal models, isolated parts of the receptor cells, and even electronic devices that detect taste and flavor are among the tools that may be used to evaluate the palatability of medications and predict compliance among pediatric populations.

Although there are no easy solutions to this dilemma, children's acceptance of many medicines can be improved by applying the knowledge gleaned from basic research in the chemical senses. Further development and validation of sensory methods will provide a better understanding of the sensory world of the child. This understanding, combined with new technologies and results of animal model studies, will enhance drug acceptance and compliance in pediatric populations. A better understanding of the scientific basis for distaste and how to ameliorate it is a public health priority.